The Cytotoxicity and Mechanisms of 1,2-naphthoquinone Thiosemicarbazone and Its Metal Derivatives against Mcf-7 Human Breast Cancer Cells

Author

Junnan Chen
Yue-wern Huang, Missouri University of Science and TechnologyFollow
Guanshu Liu
Zahra Afrasiabi Navan, Missouri University of Science and TechnologyFollow
Ekkehard Sinn, Missouri University of Science and TechnologyFollow
Subhash B. Padhyé
Yinfa Ma, Missouri University of Science and TechnologyFollow

Abstract

We have investigated the antitumor functions and mechanisms of 1,2-naphthoquinone-2-thiosemicarbazone (NQTS) and its metal complexes (Cu ²⁺, Pd²⁺, and Ni²⁺) against MCF-7 human breast cancer cells. The cells were dosed with these complexes at varying concentrations, and cell viability was measured by a sulforhodamine B (SRB) method. To study mechanisms of action, the complexes were incubated with topoisomerase II (topo II) and supercoiled DNA, linear DNA, nicked open DNA, and relaxed DNA were detected by agarose gel electrophoresis. The results revealed that these complexes are effective antitumor chemicals in inhibiting MCF-7 cell growth, with Ni-NQTS being the most effective among the complexes studied. Our data also indicated that Ni-NQTS is more effective than the commercial antitumor drug, etoposide, based on IC₅₀ values. The mechanistic study of action showed that metal complexes of NQTS, NQ, and NQTS can only stabilize the single-strand nicked DNA, but not double-strand breakage intermediates. In addition, metal derivatives of these ligands, but not the parent NQ and NQTS, exerted an antagonizing effect on topoisomerase II activity. In summary, chemicals with or without metal derivatives might possess different chemical-topoisomerase II-DNA interactions.

Recommended Citation

J. Chen et al., "The Cytotoxicity and Mechanisms of 1,2-naphthoquinone Thiosemicarbazone and Its Metal Derivatives against Mcf-7 Human Breast Cancer Cells," Toxicology and Applied Pharmacology, vol. 197, no. 1, pp. 40 - 48, Elsevier, May 2004.

The definitive version is available at https://doi.org/10.1016/j.taap.2004.02.004

Department(s)

Biological Sciences

Second Department

Chemistry

Keywords and Phrases

1,2 naphthoquinone thiosemicarbazone; etoposide; thiosemicarbazone derivative; unclassified drug; antineoplastic activity; breast cancer; cancer cell; cell viability; complex formation; controlled study; cytotoxicity; drug mechanism; enzyme activity; human; human cell; IC 50; ligand binding; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; DNA Topoisomerases, Type II; DNA, Neoplasm; Dose-Response Relationship, Drug; Female; Humans; In Situ Nick-End Labeling; Indicators and Reagents; Metals; Naphthoquinones; Mink cell focus-forming virus

International Standard Serial Number (ISSN)

0041-008X

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2004 Elsevier, All rights reserved.

Publication Date

15 May 2004